| Primary Identifier | IPR002959 | Type | Family |
| Short Name | TNF_alpha |
| description | Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [, , ]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [, ]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine []. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers []. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [].There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The structure of human TNF has been determined to 2.9 A using X-ray crystallography. The protein is trimeric, each subunit consisting of an anti-parallel β-sandwich. The subunits trimerise via a novel edge-to-face packing ofβ-sheets []. It is believed that each TNF molecule has three receptor-interaction sites (between the three subunits), thus allowingsignal transmission by receptor clustering []. This entry represents TNF-alpha, which is a soluble cytokine with a wide variety of functions: it causesdamage to tumour cells but has no effect on normal cells; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by directaction or by stimulation of interleukin-1 secretion; and it can stimulatecell proliferation and induce cell differentiation under certain conditions. |
